(Top) TRPV1 activation leads to cation influx, depolarizing the neuron; in addition, calcium entering the cell activates ANO1 to stimulate chloride efflux, causing further depolarization. (Bottom) The increased depolarization produced by ANO1 activation leads to an increase in glutamate release at the nerve terminal and enhanced perception of pain. (From Takayama et al., 2015.)